The incidence rates of breast cancer vary more than two-fold between Hispanic and non-Hispanic white (NHW) women; Hispanic women have worse survival after diagnosis than NHW women. We propose to evaluate these health disparities in breast cancer development and survival along the continuation of American Indian to NHW women utilizing existing resources from the 4 Corner's States, California, and Mexico City. Existing resources utilized will be behavioral and social lifestyle exposure data along with DNA obtained at the time of interview. Survival data has been ongoing and will continue to be monitored via local SEER and CDC tumor registries. Genetic and lifestyle data are available from approximately 8039 Hispanic and NHW cases of breast cancer and population-based controls. By pooling resources from three studies, we will efficiently examine a biological pathway that we believe is important to breast cancer development and survival and that influences differences in breast cancer rates among Hispanic and NHW women. Evaluation of genetic factors will focus on a pathway that appears to work in conjunction with insulin-, estrogen-, and inflammation-related pathways and represents a point of convergence. This pathway, which we call the Convergence of Hormones, Inflammation, and Energy Functioning (CHIEF) Signaling Pathway has not been studied comprehensively in either Hispanic or non-Hispanic white women and will include genes to be studied include SOC1, SOC2, AKT, FRAP1(alias mTOR), P13K, STK11, AMP, PTEN, VEGF, & S6K1,S6K2, CRP, NFKB, IKB, IL10, IL8, IL6, TNFalpha using an Illumina platform. Breast cancer associations will be tested between genetic polymorphisms and haplotypes of these genes in Hispanic and NHW women and by proportion of American Indian ancestry. Interaction of signaling pathway genes with each other and with NSAIDs, aspirin, BMI, estrogen, and physical activity will be examined. These genetic factors will be evaluated with survival to determine their contribution to survival differences observed for Hispanic and NHW women. PUBLIC HEALTH RELEVANCE: This study will advance our understanding of breast cancer etiology in Hispanic and American Indian women as well as women overall. The contrast between high and low risk populations will enhance this effort in a cost-efficient manner. Results could identify potential targets for drug therapy.